1. Field of the Invention
The present invention relates to a quantitative analyzer for measuring such as a glucose level of biological fluid, particularly body fluid.
2. Description of the Prior Art
Various biosensors utilizing a specific catalytic action possessed by enzymes have recently been developed and applied, in particular, in the clinical field. Development of biosensors having an ability of providing rapid and yet precise analytical results have long been desired in view of increasing number of samples and increasing number of items to be tested.
Diabetes mellitus is a disease from which the patient can not completely recover. However, the patient can live a normal life by keeping a concentration of glucose in blood at a normal level. Accordingly, constant retention of the normal glucose level is essential as a treatment of diabetes mellitus. The retention of the normal glucose level may be easily carried out on inpatients under physician's observation.
However, outpatients must conduct self-management in order to keep their blood glucose at a constant normal level. Such self-management includes dietary therapy, ergotherapy, and drug therapy, and the patients usually conduct the self-management on the above-noted two or more items under physician's directions. It is reported that when patients can check by themselves if their blood glucose level analytical results of glucose level in blood is within normal range or not, the self-management can be more effective.
In the treatment of insulin-dependent diabetes mellitus (IDDM), normal blood glucose level is maintained through repeated insulin-injections effected by patients themselves. However, the blood glucose level varies rapidly and considerably depending on caloric intake, dietary time, and injection time, and therefore, it is essential that the patients conduct the measurement of the glucose level by themselves.
Under such circumstances, various portable measurement systems have long been commercially available, which enable diabetes patients to conduct the glucose level measurement by themselves. Blood glucose level is generally determined using such a conventional measurement system in the following manner: whole blood which has been taken from a fingertip or ear lobe using a needle is contacted a test paper containing an enzyme specifically reacting with glucose and a color-producing reagent which develops color based on oxidation-reduction reaction; thereby the reagent and blood glucose react together and produce color, a thickness of which is measured using an exclusive mini-reflectometer analyzer attached to the system; the blood glucose level is determined on the basis of the calibration curve previously prepared and memorized in the analyzer.
However, it has been found that the blood glucose level determined according to the above systems varies greatly depending on patients' manipulation for measurement. Accordingly, Diabetes Associations in many countries have counseled the improvement of the measurement systems. The most important factor causing the above-noted variation of test results is associated with the manipulation needed for removing excessive blood from the test paper after a predetermined time. The removal of excessive blood is usually conducted through wiping with absorbent cotton, removing with a filter paper or rinsing with water, and such procedures bring about test errors in the following manner.
(i) Remaining blood on the test paper due to incomplete removal gives a greater value than the actual value. PA1 (ii) Excessive wiping or rinsing damages the test paper or washes out colored reagent, which gives smaller value than the actual value. PA1 (iii) Inadequate manipulation which brings about shortage of reaction time causes insufficient coloration of the reagent, and mistimed manipulation makes it impossible to completely remove blood because of blood clotting or drying, thereby erroneous test results are obtained.
Moreover, when blood is contacted with the test paper, the command (key input) of the timing for starting the measurement should be effected within an elapse of mistiming from .+-.2 to 3 seconds. In actual cases (of some patients), however, this mistiming may be 30 seconds to one minute, which can be another factor for the variation of test results, causing less reliability of measured values.
In the last few years there has been commercially available a new measurement system (manufactured by Medisense Inc., commodity name: Exactech) which has solved a main part of the above problems. This system is a pen type system which displays measuring results 30 seconds after its measurement start switch is pressed the moment blood is fed onto its test electrode chip. The system has obviated the need of removing blood and the factors for considerable test errors.
Diabetics, in some cases, have poor blood circulation and are therefore susceptible to infectious disease. This means that a slight wound on their hands or feet may cause suppuration, thus requiring the diabetics to keep themselves clean. Accordingly, equipment and a sensor for collecting blood in the measurement of blood glucose level are preferably provided in disposable form in view of hygienic control rather than used a plurality of times after they are sterilized and stored. This will ensure safety in hygiene and alleviate patients' burden.
As a method that allows a sensor to be disposable, a biosensor has already been proposed which is disclosed in the Japanese Patent Laid Open 61-294351. This biosensor, as shown in FIG. 1, is so constructed that electrode systems 136(136'), 137(137'), and 138(138') made of carbon or the like are formed on an insulating substrate 135 by a method of screen printing or the like, an insulating layer 139 is provided thereon, the electrode systems are covered with a porous body 141 carrying oxidoreductase and electron acceptors, and all these are integrated with a retaining frame 140 and a cover 142. When a sample liquid is dropped onto the porous body, the oxidoreductase and electron acceptors carried by the porous body are dissolved in the sample liquid, causing a reaction to proceed between the enzyme and substrate in the liquid and the electron acceptors to be reduced. After completion of the reaction, the reduced electron acceptors are electrochemically oxidized, and the resulting value of oxidation current is used to determine the concentration of substrate in the sample liquid.
However, in the Exactech, it is necessary to press the measurement start switch, which causes a defect that a considerable extent of mistiming in the measurement cannot be prevented. Moreover, its analyzer, being of pen type, makes its switch formed into one. As a result, since the calibration and adjustment of the analyzer must be carried out using this switch, the key operation involved has been made more complex unexpectedly. Also, since blood is placed onto the test electrode chips tipped by the pen and measurement is conducted without wiping the blood off, the patient is required to keep holding the analyzer during measurement so that the blood will not spill out. The system has therefore been inconvenient to use for the patients.
As described heretofore, since the self-management measurement system of blood glucose level conventionally available requires patients to conduct the command of starting measurement by themselves, it has been accompanied by such a defect that correct test results cannot be obtained depending on patients, manipulation. Moreover, complex key operation has been involved in operation for the calibration and test of the analyzer.
Conventional disposable systems, on the other hand, have been accompanied by such problems that test results may vary or that patients are required to distinguish whether a sensor has already been used or not.